The specific aim of this proposal is to test the feasibility of developing a long-lasting, implantable probe for rapid measurement of multiple neurochemicals in the brain. Currently, neuroscience research is limited to three techniques for measuring the concentrations of neurochemicals in vivo; microdialysis to obtain average concentrations over a relatively long time period (5-20 minutes), enzyme-based biosensors to detect a single neurochemical every second over a relatively large spatial area (500 m length electrode), and carbon-fiber microelectrodes to detect dopamine with fast scan cyclic voltammetry (FSCV). A new tool is required for rapid detection of concentrations of multiple neurochemicals with spatial resolution on the cellular level. Such a tool would allow neuroscience researchers to ask new questions about the mechanisms behind disease states and behaviors, such as drug consumption. The proposed neural probe fulfills this need by detecting two neurochemicals every 4 seconds with 50 m spatial resolution. The proposed probe will detect cocaine and substance P, a neuropeptide implied in cocaine addiction (Kampman, 2010). In 2008, reports stated that 1.4 million Americans meet the criteria for abuse or dependence on cocaine, which is associated with violence and incarceration (NIDA 2010; Nyamathi et al., 2012). SB Microsystems has already developed a proprietary MEMS process for fabricating implantable, multi-site neural probes for studying the rat brain. Our existing probes have the feature size necessary for a 10-fold spatial resolution improvement over the available enzyme-based electrodes. The proposed probe will build on our existing platform by functionalizing the probe site surfaces with molecules for the detection of specific neurochemicals. Detection of multiple neurochemicals will be achieved by patterning different neurochemical- specific detection molecules onto adjacent probe sites. Our Phase I proposal will determine feasibility for commercialization of these probes by; 1) improving functionalized probe fabrication by adjusting aptamer molecule modifications, immobilization technique, and electrical signal detection to achieve the best possible sensitivity and time response and 2) developing a Potentiostat circuit based for detection. Next, we will 3) functionalize the probe to detect multiple analytes with the cocaine and substance P aptamers and 4) implant probes into rats for in vivo data collection. Success in this Phase I feasibility study will be determined by te accurate detection of physiologically relevant concentrations of cocaine and substance P by probes that are stable in vivo for 2 days. In Phase II, we plan to develop more aptamers that can be applied to our probes for the detection of more than 2 neurotransmitters. We will use principles of robust design to turn our prototype into a commercial product. The attached letters of support indicate that we may be able to sell a successful prototype from Phase I to neuroscience researchers.